Respiratory syncytial virus (RSV) is a major cause of lower respiratory tract disease in infants, young children and the elderly, particularly those that are institutionalized. It is the most common cause of viral bronchiolitis and pneumonia in children, and outbreaks in the United States frequently reach epidemic proportions during the winter months, accounting for roughly 90,000 hospitalizations and 4500 deaths per year. Gemini Technologies Inc. is developing novel antisense compounds for use in the treatment of RSV infections. These compounds are comprised of an antisense component and an activator moiety, called 2',5'- oligoadenylate or 2-5A. The antisense component provides specificity, and directs the compound to the targeted viral RNA genome, while the 2- 5A portionof the chimera attracts and activates Rnase L, a potent endoribonuclease that can cleave the genomic RNA strands directly. We have developed an early stage 2-5A anti-RSV compound that is a potent inhibitor of RSV replication in cultured cells. Our goal is to improve upon the efficacy of this compound by increasing its stability, affinity for target RNA, and antiviral potential in preparation for preclinical animal studies. If these studies are successful, the resulting compound should fill an important void by providing a safe and effective therapeutic for the fight against RSV. PROPOSED COMMERCIAL APPLICATIONS: RSV is a major health concern in the United States. The proposed studies seek to improve upon our lead antiRSV 2-5A antisense compound, which has the potential to be more efficacious and less toxic than.the RSV therapeutics currently on the market. The proposed compound- optimization studies also offer the potential to dramatically improve the overall efficacy of the 2-5A antisense approach since the results can be applied to other therapeutics currently under development by our company.